| Summary: | <b>Background/Objectives:</b> Pneumococcal conjugate vaccines (PCVs) have significantly reduced invasive pneumococcal disease (IPD) globally. We conducted a systematic review to assess whether serotype and antimicrobial resistance trends in the Middle East and North Africa (MENA) reflect global patterns post-PCV introduction. <b>Methods:</b> We searched the CINAHL, MEDLINE, PUBMED, EMBASE, Global Health, Global Index Medicus, EBSCO, Scopus, and Cochrane databases for articles published from inception to 24 January 2024. Eligible studies were original articles in English or French, reporting IPD serotype distribution or antimicrobial susceptibility in the MENA region. Risk of bias was assessed using the STROBE checklist. <b>Results:</b> Eighty-nine studies from 18 countries were included. A decline in PCV7 serotypes was observed following the introduction of PCV10 or PCV13, which was more pronounced in PCV10-era studies. Serotype 3 increased post-PCV13 era, while 19A declined only after PCV10. An expansion in PCV20 serotypes and non-vaccine types (NVTs) was noted in PCV13-implementing countries. Antimicrobial resistance data were insufficient to provide a reliable trend. <b>Limitations:</b> There was limited AMR data and variable surveillance quality across countries. <b>Conclusions:</b> PCV introduction resulted in a modest decrease in PCV7 serotypes and a variable impact on PCV13 serotypes. This, along with the increase in PCV20 serotypes, indicates that higher-valency PCVs might provide better serotype coverage in the region. The study highlights the need for more robust surveillance across the region. <b>Registration:</b> CRD42018104529.
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